Abstract

Arthritogenic alphaviruses, such as Ross River virus (RRV) are associated with worldwide outbreaks of human polyarthritis/arthralgia. The pathogenesis of RRV and other alphaviruses is poorly understood. Studies have shown potential links between the different strains of RRV and variation in their pathogenesis and virulence. Currently there is believed to be two circulating strains of RRV, the south western (SW) from the south west region of Western Australia and the north eastern (NE) from the east coast of Australia. Studies have suggested that the persistence of RRV may be the result of an impaired immune response. This study was designed to determine if the SW and NE isolates of RRV have the ability to induce apoptosis in DCs and fibroblasts and discover any possible variation in their apoptosis-inducing capacity. Both Vero cells and murine bone marrow DCs (BMDCs) were infected with the SW74249 (SW) and SW82627 (NE) strains of RRV. A time course analysis of two apoptotic markers and a cell viability marker for both cell types was conducted by flow cytometry. The results indicate RRV- induced apoptosis in both Vero cells and BMDCs, with RRV inducing a stronger pro-apoptotic response in BMDCs than Vero cells, 24 h after infection. Between the two strains there was little variation in the Vero cells over time. In the BMDCs there was some variation with the RRV-SW strain inducing a higher percentage of cell death than the RRV-NE strain, 24 h after infection. Collectively, the data indicates that RRV has the capacity to induce a pro-apoptotic response in DCs, with the SW presenting as more aggressive compared to the NE, potentially leading to greater virulence. This data could help to explain the mechanism of RRV persistence in vertebrate hosts, as well as the reported differences in severity and duration of human clinical symptoms. Immunotherapy aimed at correcting the patient’s dysfunctional immune system, may represent a new strategy for the successful medical treatment of RRV infection.